Fluorination with aminosulfur trifluorides

ABSTRACT

A fluorination method of oxygen and halogen sites with diaryl-, dialkoxyalkyl-, alkylalkoxyalkyl-, arylalkoxyalkyl- and cyclic aminosulfur trifluorides fluorinating reagents is disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation-in-part of U.S. patent application Ser. No.08/939,940 filed Sep. 29, 1997 now U.S. Pat. No. 6,080,886.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not applicable.

BACKGROUND OF THE INVENTION

The development of safe, efficient, and simple methods for selectiveincorporation of fluorine into organic compounds has become a veryimportant area of technology. This is due to the fact that fluorinestrategically positioned at sites of synthetic drugs and agrochemicalproducts significantly modifies and enhances their biologicalactivities. The conversion of the C—O to the C—F bond, which is referredto herein a deoxofluorination, represents a viable method to produceselectively fluorinated organic compounds, but the low yields andhazards associated with the current deoxofluorination reagents andprocesses severely limit the application of this technique.

The introduction of fluorine into medicinal and agrochemical productscan profoundly alter their biological properties. Fluorine mimicshydrogen with respect to steric requirements and contributes to analteration of the electronic properties of the molecule. Increasedlipophilicity and oxidative and thermal stabilities have been observedin such fluorine-containing compounds.

In view of the importance of organofluorine compounds, efforts aimed atthe development of simple, safe, and efficient methods for theirsynthesis have escalated in recent years. The conversion of thecarbon-oxygen to the carbon-fluorine bond by nucleophilic fluorinatingsources (deoxofluorination) represents one such technique which has beenwidely used for the selective introduction of fluorine into organiccompounds. A list of the deoxofluorination methods practiced to dateincludes: nucleophilic substitution via the fluoride anion; phenylsulfurtrifluoride; fluoroalkylamines; sulfur tetrafluoride; SeF₄; WF₆;difluorophosphoranes and the dialkylaminosulfur trifluorides (DAST). Themost common reagent of this class is diethylaminosulfur trifluoride,Et-DAST or simply DAST.

The DAST compounds have proven to be useful reagents for effectingdeoxofluorinations. These reagents are conventionally prepared byreaction of N-silyl derivatives of 2° amines with SF₄. In contrast toSF₄, they are liquids which can be used at atmospheric pressure and atnear ambient to relatively low temperature (room temperature or below)for most applications. Deoxofluorination of alcohols and ketones areparticularly facile and reactions can be carried out in a variety oforganic solvents (e.g., CHCl₃, CFCl₃, glyme, diglyme, CH₂Cl₂,hydrocarbons, etc.). Most fluorinations of alcohols are done at −78° C.to room temperature. Various functional groups are tolerated includingCN, CONR₂, COOR (where R is an alkyl group), and successfulfluorinations have been accomplished with primary, secondary andtertiary (1°, 2°, 3°) allylic and benzylic alcohols. The carbonyl togem-difluoride transformation is usually carried out at room temperatureor higher. Numerous structurally diverse aldehydes and ketones have beensuccessfully fluorinated with DAST. These include acyclic, cyclic, andaromatic compounds. Elimination does occur to a certain extent whenaldehydes and ketones are fluorinated and olefinic by-products are alsoobserved in these instances.

While the DAST compounds have shown versatility in effectingdeoxofluorinations, there are several well recognized limitationsassociated with their use. The compounds can decompose violently andwhile adequate for laboratory synthesis, they are not practical forlarge scale industrial use. In some instances, undesirable by-productsare formed during the fluorination process. Olefin eliminationby-products have been observed in the fluorination of some alcohols.Often, acid-catalyzed decomposition products are obtained. The reagent'stwo step method used for their synthesis renders these relatively costlycompositions only suitable for small scale syntheses.

The DAST reagents are recognized as fluorinating reagents in U.S. Pat.Nos. 3,914,265 and 3,976,691. Additionally, Et-DAST and relatedcompounds have been discussed in W. J. Middleton, New FluorinatingReagents. Dialkylaminosulfur Fluorides, J. Org. Chem., Vol. 40, No. 5,(1975), pp 574-578. However, as reported by Messina, et al., AminosulfurTrifluorides: Relative Thermal Stability, Journal of Fluorine Chemistry,43, (1989), pp 137-143, these compounds can be problematic fluorinatingreagents due to their tendency to undergo catastrophic decomposition(explosion or detonation) on heating. See also reports on this by J.Cochran, Laboratory Explosions, Chemical and Engineering News, (1979),vol. 57, No. 12, pp. 4 & 74; and W. T. Middleton, Explosive Hazards withDAST, Chemical and Engineering News, (1979), vol. 57, No. 21, p. 43.Difficulties with major amounts of by-products in the fluorinationreaction is also noted. See also M. Hudlicky, Fluorination withDiethylaminosulfur Trifluoride and Related Aminofluorosulfuranes,Organic Reaction, Vol. 35, (1988), pp 513-553.

Further, Russian Inventor's Certificate No. 433,136 published Dec. 15,1974 discloses sulfur dialkyl(alkylaryl)aminotrifluorides.

G. L. Hann, et. al., in Synthesis and EnantioselectiveFluorodehydroxylation Reactions of(S)-2-(Methoxymethyl)pyrrolidin-1-ylsulphur Trifluoride, the FirstHomochiral Aminofluorosulphurane, J. Chem. Soc., Chem. Commun. (1989) pp1650-1651, disclosed the aminosulfur trifluorides,(S)-2-(methoxymethyl)pyrrolidin-1-ylsulphur trifluoride andN-morpholinosulphur trifluoride as fluorinating reagents for2-(trimethylsiloxy)octane.

The method and compositions of the present invention overcome thedrawbacks of the prior art fluorinating reagents, including DAST, byproviding more thermally stable fluorine bearing compounds which haveeffective fluorinating capability with far less potential of violentdecomposition and attendant high gaseous by-product evolvement, withsimpler and more efficient fluorinations, as will be set forth ingreater detail below.

BRIEF SUMMARY OF THE INVENTION

The present invention is a method for the fluorination of a compoundusing a fluorinating reagent comprising contacting the compound with thefluorinating reagent under conditions sufficient to fluorinate thecompound wherein the fluorinating reagent is an aminosulfur trifluoridecomposition having a structure with one or more:

wherein m=1-5 and R¹ and R² are:

(1) when m=1, individually aryl or meta- or para-substituted arylradicals in which the meta- or para-substitution is selected from thegroup consisting of normal and branched C₁₋₁₀, trifluoromethyl, alkoxy,aryl C₆₋₁₀, nitro, sulfonic ester, N,N-dialkylamino and halogens; or

(2) when m=1, individually aryl radicals which are fused or linked toone another; or

(3) when m=1, one of R¹ and R² is an aryl radical and the other is an atleast 5 member saturated cyclic hydrocarbon radical having zero to threeheteroatoms selected from the group consisting of oxygen, nitrogen andmixtures thereof; or

(4) when m=1, one of R¹ and R² is an aryl radical and the other is an atleast 5 member saturated cyclic hydrocarbon radical having zero to threeheteroatoms selected from the group consisting of oxygen, nitrogen andmixtures thereof wherein said cyclic hydrocarbon radical is fused tosaid aryl radical; or

(5) when m=1, together a cyclic ring having 2 to 10 carbon ring membersand 1 heteroatom selected from the group consisting of oxygen, nitrogenand alkylated nitrogen wherein said ring has 1 to 2 alkoxyalkylfunctionalities; or

(6) when m=1, together an unsaturated cyclic ring having 2 to 4 carbonring members and one to three heteroatoms selected from the groupconsisting of oxygen, nitrogen, protonated nitrogen and alkylatednitrogen wherein said ring has one to three functional groups selectedfrom hydrogen, normal and branched C₁₋₁₀ alkyl, haloalkyl, alkoxy, arylhalogen, cyano, nitro and amino; or

(7) when m=1, individually alkoxyalkyl radicals; or

(8) when m=1, one of R¹ and R² is alkoxyalkyl and the other is selectedfrom the group consisting of alkyl and aryl radicals; or

(9) when m=2-5, R¹ is a single phenyl radical linked to each —NSF₃radical and R² is an aryl radical having C₆ to C₁₀; or

(10) when m=2-5, R¹ and R² are individually divalent aryl radicals of C₆to C₁₀ linked to adjacent —NSF₃ radicals except R¹ and R² are monovalentaryl radicals having C₆ to C₁₀ where R¹ and R² are linked to only one—NSF₃ radical; or

(11) when m=1, one of R¹ and R² is an aryl radical and the other is analkyl radical of C₁₋₁₀.

Preferably, the compound being fluorinated is selected from the groupconsisting of alcohols, carboxylic acids, aldehydes, ketones, carboxylicacid halides, sulfoxides, phosphonic acids, sulfinyl halides, sulfonicacids, sulfonylhalides, silylhalides, silyl ethers of alcohols,epoxides, phosphines, thiophosphines, sulfides and mixtures thereof.

Preferably, the composition used as the fluorinating reagent has thestructure:

(R¹)(R²)(R³)CO(R⁴)N(SF₃)(R⁵)OC(R⁶)(R⁷)(R⁸)

wherein R^(1-3, 6-8) are individually H, normal or branched alkyl C₁₋₁₀or aryl C₆₋₁₀ and R⁴⁻⁵ are C₂₋₁₀ normal or branched alkyl.

Alternatively, the composition used as the fluorinating reagent has thestructure:

R³OR⁴N(SF₃)R⁵OR⁶

wherein R³ and R⁶ are individually C₁ to C₁₀ in a normal or branchedchain alkyl and R⁴ and R⁵ are C₂₋₁₀ normal or branched alkyl.

More preferably, the composition used as the fluorinating reagent hasthe structure:

CH₃OCH₂CH₂N(SF₃)CH₂CH₂OCH₃

Preferably the fluorination is conducted in the presence of a solvent.

More preferably, solvent is selected from the group consisting ofparaffins, halocarbons, ethers, nitriles, nitro compounds and mixturesthereof.

Preferably, the fluorination is conducted under anhydrous conditions.

Preferably, the fluorination is conducted at a temperature above thefreezing point of said solvent and below the boiling point of saidsolvent.

Alternatively, when the compound is a ketone, the fluorination iscatalyzed with at least a catalytic amount of a Lewis acid.

Preferably, the Lewis acid is selected from the group consisting of BF₃,Znl₂, TiCl₄ and mixtures thereof.

Alternatively, when the compound is a ketone, at least a catalyticamount of HF is added to the fluorination.

Preferably the alcohol is selected from the group consisting ofmonofunctional and polyfunctional primary, secondary, tertiary and vinylalcohols and mixtures thereof.

Preferably, the carboxylic acid is selected from the group consisting ofaliphatic, aromatic and heterocyclic carboxylic acids and mixturesthereof.

Preferably, the aldehyde is selected from the group consisting ofaliphatic, aromatic and heterocyclic aldehydes and mixtures thereof.

Preferably, the ketone is selected from the group consisting ofaliphatic, aromatic and heterocyclic ketones and mixtures thereof.

Preferably, the carboxylic acid halide is selected from the groupconsisting of aliphatic, aromatic and heterocyclic carboxylic acidhalides of chlorine, bromine and iodine and mixtures thereof.

Preferably, the sulfoxide is selected from the group consisting ofaliphatic, aromatic and heterocyclic sulfoxides having adjacent hydrogenatoms and mixtures thereof.

Preferably, the phosphonic acid is selected from the group consisting ofaliphatic, aromatic and heterocyclic phosphonic acids and mixturesthereof.

Preferably, the sulfinyl halide is selected from the group consisting ofaliphatic, aromatic and heterocyclic sulfinyl halides of chlorine,bromine and iodine and mixtures thereof.

Preferably, the sulfonic acid is selected from the group consisting ofaliphatic, aromatic and heterocyclic sulfonic acids and mixturesthereof.

Preferably, the sulfonyl halide is selected from the group consisting ofaliphatic, aromatic and heterocyclic sulfonyl halides of chlorine,bromine and iodine and mixtures thereof.

Preferably, the silyl halide is selected from the group consisting ofaliphatic, aromatic and heterocyclic silyl halides of chlorine, bromineand iodine and mixtures thereof.

Preferably, the silyl ether of alcohol is selected from the groupconsisting of silyl ethers of primary, secondary and tertiary alcoholsand mixtures thereof.

Preferably, the epoxide is selected from the group consisting ofaliphatic, aromatic and heterocyclic epoxide and mixtures thereof.

Preferably, the phosphine is selected from the group consisting ofaliphatic, aromatic and heterocyclic phosphines and mixtures thereof.

Preferably, the thiophosphine is selected from the group consisting ofaliphatic, aromatic and heterocyclic thiophosphines and mixturesthereof.

Preferably, the sulfide is selected from the group consisting ofaliphatic, aromatic and heterocyclic sulfides with adjacent hydrogensand mixtures thereof.

In a preferred embodiment, the present invention is a method for thefluorination of a compound using a fluorinating reagent comprising anaminosulfur trifluoride composition comprising synthesizing theaminosulfur trifluoride composition with a secondary amine and SF₄ andwithout isolating said aminosulfur trifluoride composition, fluorinatingsaid compound with said aminosulfur trifluoride composition.

Preferably, the synthesis is performed in the presence of a tertiaryamine.

Preferably, the aminosulfur trifluoride is a dialkyl aminosulfurtrifluoride, more preferably, diethylaminosulfur trifluoride.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

Not Applicable

DETAILED DESCRIPTION OF THE INVENTION

A novel fluorination method using several novel aminosulfur trifluoridesis presented in this invention. These compositions have been shown to bevery efficient and useful for effecting deoxofluorination of alcoholsand ketones. In addition, thermal analysis studies indicate that theyshould be much safer to use in the present fluorination method than thecurrently available dialkylaminosulfur trifluorides (DAST).

The simplicity of the method used for preparing the new aminosulfurtrifluorides, as described hereafter, combined with their relativesafety in use in the present invention should make this fluorinationmethod attractive for large scale production of fluorinated products.

Fluorinating Reagents for the Present Method

The compositions useful in the present fluorination method areidentified as follows by several general classes, including: Diarylsystems, alkoxyalkyl aminosulfur trifluorides and arylalkylaminosulfurtrifluorides.

1. Diaryl Compositions

ArN(SF₃)Ar′

where Ar and Ar′ are the same or different aryl groups (i.e., mixedcompositions). The aryl groups can be mono or polynuclear, the latterencompassing isolated ring or fused-ring groups and each contemplatessubstituted aryl groups.

For example, when both groups are derived from benzene, the generalformula is:

a) R¹ and R² represent one or more substituents (like or different).Examples provided (Table 1) for R¹, R²=H, p-Cl, p-OCH3, p-CH3. Thesegroups may be para or meta to the NSF₃ group. R¹, R² can additionally beOR (R=alkyl or aryl), Br, I, F, alkyl or aryl groups, CF₃, NO₂, SO₃R(R=alkyl or aryl), NR₂ (R=alkyl or aryl). These groups may be ortho,meta or para to the NSF₃ group.

b) Aryl naphthyl compositions (Table 1)

c) Fused or linked diaryl compositions, e.g.,

n=2 or more

Furthermore, oligomeric or polymeric analogues may be used in whicharomatic units are linked via the nitrogen of the NSF₃ group, such as:

where y=0-6 and x=1-1000

d) Heteroatom (O,N) containing aromatic compositions (branched or fused)

wherein R³ is an aryl radical of C₆ to C₁₀, n=1-5, R¹ and R² areindividually H or alkyl C₁₋₁₀ and X=zero to three ring elementsubstitutions at any available position on the ring of O or NR⁴ whereR⁴=H, normal or branched alkyl C₁₋₁₀.

wherein R¹ and R²=individually H or normal or branched alkyl C₁₋₁₀.n=1-5 and X=zero to three ring element substitutions at any availableposition on the ring of O or NR³ where R³=H, normal or branched alkylC₁₋₁₀.

One of the aromatic ring groups attached to the N—SF3 group may be5-membered or greater and contain heteroatoms such as O(1-3) or N(1-3).The heteroatom-containing ring may be branched from the N—SF3 group orfused to the other aromatic ring (Ar).

2. Alkoxyalkylamine Compositions

Alkyl=normal or branched C₁₋₁₀. Alkoxyalkyl=(a) —R¹—O—R², where R¹ isC₂₋₁₀ normal or branched alkyl and R² is C₁₋₁₀ normal or branched alkylor (b) —(R³—O)_(n)—R², where R² is C₁₋₁₀ normal or branched alkyl and R³is C₂₋₃ normal or branched alkyl and n=1-10.

d) Alkoxyalkyl branched from ring compositions containing NSF₃

wherein R¹ and R⁶ are individually normal or branched alkyl C₁₋₁₀, R²⁻⁵,are individually H or normal or branched alkyl C₁₋₁₀, m=1-10, n=1-10,and p=1-10.

e) Alkoxyalkyl branched heteroatom ring compositions containing NSF₃

wherein R¹ and R⁶ are individually normal or branched alkyl C₁₋₁₀, R²⁻⁵,are individually H, or normal or branched alkyl C₁₋₁₀, m=1-10, n=1-10,and p=1-10, and X=a ring element substitution at any available positionof the ring of O or NR⁷ where R⁷=H, normal or branched alkyl C₁₋₁₀.

where m=1-10, n=1-10, R¹ and R²=individually H, or normal or branchedalkyl C₁₋₁₀, R³=normal or branched alkyl C₁₋₁₀ and X=a ring elementsubstitution at any available position of the ring of O, NR⁴ whereR⁴=normal or branched alkyl C₁₋₁₀.

3. Arylalkylaminosulfur trifluorides

N-methyl, N-phenyl aminosulfur trifluoride exemplifies this group.

A preferred class of deoxofluorination reagents has the generalstructure:

(R¹)(R²)(R³)CO(R⁴)N(SF₃)(R⁵)OC(R⁶)(R⁷)(R⁸)

wherein R^(1-3, 6-8) are individually H, normal or branched alkyl C₁₋₁₀or aryl C₆₋₁₀ and R⁴⁻⁵ are normal or branched C₂₋₁₀. A more specificclass of preferred deoxofluorination reagents has the general structure:

R³OR⁴N(SF₃)R⁵OR⁶

wherein R³ and R⁶ are individually C₁ to C₁₀ normal or branched chain,R⁴⁻⁵ are C₂₋₁₀ normal or branched alkyl. More specifically thedeoxofluorination reagent has the specific structure:

CH₃OCH₂CH₂N(SF₃)CH₂CH₂OCH₃

For the purpose of this invention the following definitions areprovided. Alkyl shall mean normal and branched carbon radicals up to tencarbons. Aryl shall mean six and ten member carbon rings having aromaticcharacter. Fused aryl shall mean aromatic rings containing two commoncarbon atoms. Linked aryl shall mean aromatic rings joined together by abond from a carbon atom of one ring to a carbon atom of another ring.Heteroatoms shall mean oxygen and/or nitrogen in a carbon memberedradical. Para-substitution on an aryl ring shall include H, p-Cl,p-OCH3, p-CH3, OR (R=alkyl C₁₋₁₀ or aryl C₆₋₁₀), Br, I, F, alkyl C₁₋₁₀or aryl C₆₋₁₀ groups, NO₂, SO₃R (R=H, alkyl C₁₋₁₀ or aryl C₆₋₁₀), NR₂(R=H, alkyl C₁₋₁₀ or aryl C₆₋₁₀). Alkoxyalkyl typically means an oxygenbridging two alkyl groups, but it is also contemplated to includepolyethers, such as: —O(—RO)_(n)R′ where R and R′ are C₁₋₃ alkyl andn=1-10.

To develop thermally stable aminosulfur trifluorides for thefluorination method of the present invention, the inventors consideredcompositions which would not produce gaseous by-products ondecomposition. The production of HF via abstraction of acidic protons inthe vicinity of the N—SF₃ group by fluoride ion is believed to be onefactor which contributes to the instability of the dialkylaminosulfurtrifluorides. Consequently, compositions lacking such protons areattractive candidates for the present invention, although compositionswith such protons can be useful. In order to circumvent the thermalinstability which results from molecular disproportionation ofdialkylaminosulfur trifluoride, the inventors prepared compositionswhich possess sterically demanding groups attached to the N—SF₃function. Aminosulfur trifluorides with a highly electron deficientnitrogen bonded to the SF₃ group are also appropriate since moleculardisproportionation will be less significant in these compositions.

The diaryl, arylalkyl and alkoxyalkylaminosulfur trifluorides fulfillmost of the structural requirements for a thermally stable product for afluorination method, such as deoxofluorination. The preparation andreactions of these compositions are described below.

An attempted synthesis of diphenylaminosulfur trifluoride by theconventional reaction route of the N-trimethylsilyl derivative ofdiphenylamine with SF₄ proved to be difficult. Only a small amount ofproduct (<10% yield) was obtained in a reaction carried out at roomtemperature.

A synthetic route to dialkyl and arylalkylaminosulfur trifluoridesdescribed in Russian Inventor's Certificate No. 433,136 was used inwhich a secondary (2°) amine is reacted with SF₄ in ethyl ethercontaining triethylamine for the preparation of several noveldiarylaminosulfur trifluorides. This simple one-step process (as opposedto the two-step method via a silyl amine) afforded a virtualquantitative yield of products at temperatures ranging from −10° C. toroom temperature. Table 1 summarizes the diaryl compositions which wereprepared by this method. The procedure proved to be particularly usefulfor the preparation of diarylaminosulfur trifluorides bearing bothelectron withdrawing and electron donating groups at the para positionof the aromatic rings. The sterically hindered N-phenyl-N-naphthyl-aminewas successfully converted to the diarylaminosulfur trifluoride at roomtemperature. However, the preparation of diarylaminosulfur trifluoridesbearing substituent groups at the ortho position of the aromatic ringproved to be more difficult. None of the desired products were obtainedin reactions carried out at −10° C. or room temperature with either2,2′-dimethyl-diphenylamine or 2,2′-dimethoxy-diphenylamine. Insteadonly starting material was recovered after several hours (3-24 h) ofreaction time. The steric hindrance imposed by the adjacent substituentgroups on the aromatic ring seems to be significant in thesecompositions.

Aminosulfur trifluorides derived from relatively electron deficientdiarylamines were found to be relatively unstable. In an attemptedpreparation of 4,4′-dichloro-diphenyl aminosulfur trifluoride, the aminewas reacted with SF₄ in ethyl ether/triethylamine (Et₂O/TEA) at 0° C.After work-up a light yellow solid was isolated. This solid productdarkened considerably on standing at room temperature (<1 h) forming4-chlorophenyl iminosulfur difluoride as the principal decompositionproduct.

The aminosulfur trifluoride is synthesized by reaction of a secondaryamine with SF₄ in a non-aqueous solvent that will not react chemicallywith SF₄ or the aminosulfur trifluoride product. Examples includeethers, e.g., ethylether (Et₂O), tetrahydrofuran (THF), halogenatedhydrocarbons, e.g., CH₂Cl₂, freons, hydrocarbons, e.g., toluene, hexane,tertiary amines, liquid SO₂ and supercritical CO₂.

The reaction can be carried out at temperatures ranging from −90° C. orthe freezing point of the solvent to the boiling point of the solvent.

The reaction mixture may be homogenous or heterogenous.

The secondary amine is represented by R¹R²NH. R¹=alkyl (cyclic ornon-cyclic, with or without heteroatoms), aryl, or alkoxyalkyl. R²=alkyl(cyclic or non-cyclic, with or without heteroatoms), aryl oralkoxyalkyl. R¹ may or may not be the same as R².

The tertiary amine is represented by R¹R²R³N. R¹, R² or R³=alkyl (cyclicor non-cyclic, with or without heteroatoms), or aryl. This includestertiary amines which contain the N-atom in a ring, e.g.,N-methylpiperidine or in a chain, e.g., triethylamine. It also includestertiary amines which contain the N-atom at a bridge-head, e.g.,quinuclidine or triethylene diamine and in fused rings, e.g.,diazabicycloundecane (DBU). Compounds containing >1, tertiary aminegroup in the molecule can also be used. The tertiary amine could alsofunction as the reaction solvent. Examples of specific amines employedfor the synthesis of R₂NSF₃ reagents should also be effective for the insitu process described below.

No aminosulfur trifluoride product was obtained when pyridine or3-methylpyridine was used instead of a tertiary amine; however, morebasic pyridines than the latter are expected to be useful.

No aminosulfur trifluoride product was obtained when NaF or CsF was usedinstead of a tertiary amine. Thus, its utilization in the process beyondsimply acting as an HF acceptor is an essential feature of theinvention.

The substrate for fluorination may be an alcohol, an aldehyde, ketone,carboxylic acid, aryl or alkyl sulfonic acid, aryl or alkyl phosphonicacid, acid chlorides, silyl chlorides, silyl ethers, sulfides,sulfoxides, epoxides, phosphines and thiophosphines.

Water or a low molecular weight alcohol (CH₃OH, C₂H₅OH, etc.) may beadded to hydrolyze the intermediate sulfinyl fluoride for disposal andto generate the starting secondary amine.

The fluorinated product may be separated from the aqueous acidic mixtureby extraction into a water immiscible organic solvent.

The desired product may be distilled and thus isolated from the crudereaction mixture.

TABLE 1 Preparation of Diarylaminosulfur trifluorides from SF₄ andDiarylamines Product Starting Material Reaction Conditions (Yield)

SF₄, Et₂O, or THF, TEA −10° C., 3 h

1 2 (quantitative)

Et₂O, or THF −10° C., 3 h

3 4 (quantitative)

Et₂O, or THF −10° C., 3 h

5 6 (quantitative)

Et₂O, or THF −10° C., 3 h

7 8 (quantitative)

Et₂O, or THF −10° C., 3 h

9 10 (quantitative)

THF −78°-RT, 3 h Starting material 11

Et₂O, −78°-RT, 3 h Starting material 12

Et₂O, −78°-RT, 3 h

13

Saturated indoles (26, 28, Table 2) afford good yields of thecorresponding aminosulfur trifluorides on reaction with SF₄ in Et₂O/TEAat −78° C. These compounds which appeared to be stable on initialpreparation decomposed rapidly on storage (<3 days).

TABLE 2 Reaction of SF₄ with heterocyclic amines in Et₂O/TEA ProductStarting material Reaction Conditions (yield)

SF₄, Et₂O, TEA −78° C. to −10° C. Tarry reaction product. No SF₃derivative 24

SF₄, Et₂O, TEA −78° C. to −10° C. Tarry reaction product. No SF₃derivative 25

SF₄, Et₂O, TEA −78° C. to −10° C.

26 27 quantitative

SF₄, Et₂O, TEA −78° C. to −10° C.

28 29 quantitative

Russian Inventor's Certificate No. 433,136 reported the preparation ofN-ethyl-N-phenylaminosulfur trifluoride in 78% yield by reaction ofN-ethyl-N-phenylamine with SF₄ in Et₂O containing tertiary (3°) amines.The present inventors confirmed these results and extended the method tothe preparation of the N-methyl analog (Table 3). The arylalkyl amineswere much more reactive towards SF₄ than the diarylamines and thereactions were completed at −78° C. with quantitative formation ofproducts. The N-ethyl-N-phenyl aminosulfur trifluoride was notidentified as a fluorinating agent. However, the present inventors foundthat this compound and related arylalkylaminosulfur trifluorides arevery advantageous in deoxofluorination reactions, as set forth below.

TABLE 3 Preparation of arylalkyl aminosulfur trifluorides ProductStarting material Reaction conditions (yield)

SF₄, Et₂O, TEA −78° C., 1 h

30 31 quantitative

SF₄, Et₂O, TEA −78° C., 1 h

32 33 quantitative

It has been further determined that dialkylaminosulfur trifluorides thatcontain an oxygen atom in the vicinity of the SF₃ group possess enhancedthermal stability. The aminosulfur trifluorides with the highestreported decomposition temperatures are N-morpholinosulfur trifluorideand (S)-2-(methoxyethyl) pyrrolidin-1-yl-sulfur trifluoride. Theincreased thermal stability of these compounds may result fromcoordination of the electron-rich oxygen atom with sulfur affording aconformationally rigid structure. However, the inventors found that(S)-2-(methoxyethyl) pyrrolidin-1-yl-sulfur trifluoride was a poorfluorinating reagent for deoxofluorination of cyclooctanol, as reportedbelow, and N-morpholino sulfurtrifluoride decomposes with the evolutionof large quantities of gas (i.e., explosively). See Table 5.

The preparation of aminosulfur trifluorides by reaction of the aminewith SF₄ in Et₂O/TEA was successfully applied to the preparation ofseveral alkoxyalkylaminosulfur trifluorides (Table 4). These includecompositions bearing one or two methoxy groups. The reactions of theprecursor amines with SF₄ were quite rapid at −78° C. affording highyields of products.

TABLE 4 Preparation of alkoxyalkyl aminosulfur trifluorides ProductStarting material Reaction conditions (Yield)

SF₄, Et₂O, TEA −78° C., 1 h

34 35 quantitative CH₃NHCH₂CH₂OMe SF₄, Et₂O, TEA CH₃N(SF₃)CH₂CH₂OMe 36−78° C., 1 h 37 quantitative

SF₄, Et₂O, TEA −78° C., 1 h

38 39 quantitative MeOCH₂CH₂NHCH₂CH₂OMe SF₄, Et₂O, TEAMeOCH₂CH₂N(SF₃)CH₂CH₂OMe 40 −78° C., 1 h 41 quantitative

Thermal analysis studies of the newly synthesized aminosulfurtrifluorides and dialkylaminosulfur trifluorides (DAST) were performedon a Radex instrument, available from Systag of Switzerland. Theinstrument is similar to ASTM E476-87. The instrument operates at aconstant heating rate (0.5 to 2.0° C./min.) and measures heat flux intoor out of a sample, in the form of a temperature difference betweensample and inert reference and also the system's total internalpressure. This provides a measure of the onset of exothermicdecomposition. The results of these studies provide useful informationabout the relative thermal stabilities of these compositions. Thedecomposition temperature and the quantity of gas (resultant gaspressure) produced on decomposition are important indicators of thesafety in use of the compositions.

Table 5 summarizes the results of the Radex thermal analysis studies andprovides a listing of decomposition temperatures, pressure gain and gasproduced on two bases for the decomposition of diaryl, dialkyl,arylalkyl, and alkoxyalkylaminosulfur trifluorides (300 mg). Higherdecomposition temperatures were recorded for the dialkyl compositions.Among the newly synthesized compositions, the alkoxyalkylaminosulfurtrifluorides decomposed at higher temperatures than the arylalkyl anddiaryl compositions.

TABLE 5 Thermal analysis of aminosulfur trifluorides by Radex Decomposi-Pressure Gain Gas tion Temp. on Decomposi- Produced Composition ° C.tion (psia) (psia/mmol Et₂NSF₃ 128 101 13 Me2NSF3 126 96.6 33

151 98.2 22

68 8.9 3

55 7.4 2

87 23.3 8

95 0 0

109 10.0 3

91 9.9 3

66 0 0 CH₃N(SF₃)CH₂CH₂OMe 104 1.5 0 37

116 16.5 5 MeOCH₂CH₂N(SF₃)CH₂CH₂OMe 108 0 0 41

A comparison of the pressure gain on decomposition indicates that thedialkyl aminosulfur trifluorides produced a significantly largerquantity of gas as compared to the other compositions. Most of thediaryl compositions produced a relatively small quantity of gas.However, N-4-chlorophenyl-N-phenylaminosulfur trifluoride was found tobe remarkably stable in this regard producing no gas on decomposition.The arylalkyl compositions produced some gas on decomposition, but thealkoxyalkylaminosulfur trifluorides evolved essentially no gas at theconditions of these tests. However, the most significant factordemonstrated by the data in Table 5 is the amount of gas produced permmol of deoxofluorination reagent tested. This is a measure of thepotential for dangerous results based upon explosion of the reagent fora normalized amount of each reagent for comparison purposes. Thereagents of the present invention showed significant improvement overthe prior art compositions.

These results indicate that the novel aminosulfur trifluorides preparedshould be much safer to use than the previously known DAST compounds.The more stable N-4-chlorophenyl-N-phenylaminosulfur trifluoride and thealkoxyalkylaminosulfur trifluorides should be especially suitable forscale-up and large scale use.

NMR spectra were obtained on a Bruker CP-300FT spectrometer operating at282.4 MHz (¹⁹F), 300.13 MHz (¹H). Chemical shifts were referenced toneat CFCl₃(¹⁹F) and CHCl₃(¹H).

G.C.M.S. Spectra were recorded on a HP 5890 Series 11 G.C. and 5972series mass selective detector with a HP-1 column.

All compositions in subparagraphs (1) through (10) of the Summary of theInvention are novel. There is one example in the literature of acomposition that exemplifies subparagraph (11): N-ethyl-N-phenylaminosulfurtrifluoride. It was prepared by L. N. Markovskii, et al (USSRpatent, 1974, No(II) 433136), but it was never used, or suggested foruse, as a fluorinating agent. Other members of this class (e.g., theN-methyl-N-phenyl analog) were prepared and used. (S)-2-(methoxymethyl)pyrrolidin-1-yl-sulfur trifluoride (compound 39 in Table 5) was reportedin the literature. It was only employed in the fluorination ofsilylethers. No indication or suggestion was given that the compoundshould be generally useful for the replacement of certain oxygen atomsin organic compounds, i.e., for the deoxo-fluorination of alcohols,ketones, aldehydes, etc. In fact, in the experimental work of thepresent invention, the deoxofluorination of alcohols by this compoundafforded much less yield than is obtained by fluorination using our newcompositions of aminosulfurtrifluorides. For example, only a 17% yieldof cyclooctyl fluoride was obtained on fluorination of cyclooctanol withcompound 39. In contrast yields in excess of 70% were obtained onfluorination of cyclooctanol with the novel aminosulfur trifluoridesunder the same reaction conditions. It is expected that the fluorinationof a silyl ether (which proceeds via the formation of a reactive oxygenanion, R—O⁻) will be more facile than reaction of the correspondingalcohol ROH with the —SF₃ compound.

The known N,N-dialkylaminosulfurtrifluorides, R₂NSF₃, (e.g., (C₂H₅)₂SF₃(DAST), and including those which contain O as a heteroatom such asN-morpholino sulfur-trifluoride, as well as the,bis(N,N-dialkylamino)-sulfur difluorides, are well known, usefulreagents for effecting the replacement of certain oxygen and halogen(Cl, Br, I) atoms in various classes of organic compounds with fluorine.The present inventors have found that the aminosulfur trifluoridecompounds of subparagraphs (1) to (11) are generally safer to use, andcan perform the oxygen and halogen replacement chemistry withsignificant improvements in reaction selectivity and yield of thedesired fluoro product.

All compositions under subparagraphs (1) to (11) of the Summary of theInvention, are safer to use than the dialkylaminosulfurtrifluorides, onthe basis of quantifiable thermal decomposition criteria, set forth inTable 5. These are: onset temperature of self-heating, and rate andextent of pressure increase, as measured by Radex instrumentation, andin some cases by accelerated rate calorimetry (ARC) measurements. It isbelieved that the most discerning criterion for safety in use is thepressure gain of volatiles upon decomposition, which may bequalitatively related to potential explosivity. Note that thedialkylaminosulfur-trifluorides (first 3 entries in Table 5) have farlarger values of pressure gained, as compared to compounds insubparagraphs (1) to (11).

In general, with compounds of subparagraphs (1) to (11), higher yieldsand selectivities to the desired fluoroproducts were realized, foralcohol and ketone substrates, as compared to those realizable under thesame conditions with the dialkylaminosulfurtrifluorides.

For the fluorination of cyclooctanol (a model alcohol) with DAST, W. M.Middleton reported, for the formation of cyclooctyl fluoride, a yield of70% and 30% of a cyclooctene elimination product. (Ref. J. Org. Chem.40, 574 (1975)). The data of the present invention on this reaction ofcyclooctanol, done under the same conditions, is in Table 6. Fordiphenylaminosulfurtrifluoride (first entry in Table), the yield andselectivity are comparable to those of DAST. However, all the otherreagents defined in subparagrahs (1) to (11) of the Summary of theInvention offer significantly higher yields of the desired fluoroproducts, and higher selectivities (less elimination products).

For the fluorination of 4-t-butylcyclohexanone, a model ketone, withDAST a 67% yield of 1,1-difluoro-4-t-butylcyclohexanone was obtained.The remainder, (33%) consisted of many other fluorinated by-productsincluding the vinyl fluoride: 1-t-butyl-4-fluoro-3-cyclohexene. Data forthe same ketone fluorination reaction conducted with compounds ofsubparagraphs (1) to (11) are presented in Table 7. For all thesecompounds, the only products seen (by NMR) are the1,1-difluoro-4-t-butylcyclohexane and the vinyl fluoride compound. Thereactions were remarkably (and surprisingly) clean. The desired difluorocompound is always produced in a higher yield than was seen for DAST,the remainder being only the vinyl fluoride. The difluoro to VinylFluoride ratio, e.g., 96:4 for Ph₂NSF₃ cited in Table 7, is thusequivalent to a 96% yield of the required difluoro product).

Synthesis of the novel and more stable fluorinating reagent compositionsused in the fluorination method of the present invention will now be setforth with regard to the following examples.

EXAMPLE 1 Synthesis of Aminosulfur Trifluorides

A 3-neck, 250 mL round-bottom flask was equipped with a magneticstirring bar, a N₂ inlet tube attached to dry ice condenser, a SF₄ gasinlet tube connected to a metal vacuum line manifold and a pressureequalized dropping funnel. The solvent (Et₂O or THF, 75 mL) wasintroduced into the flask via the dropping funnel and a 2° amine,corresponding to the products as specified below (25.0 mmol), dissolvedin the solvent (Et₂O or THF, 25 mL) and triethylamine (3.50 mL, 25.0mmol) were added to the dropping funnel. The condenser was cooled to−78° C. with dry ice/acetone and the solvent was cooled in like manner.A 1 liter ballast in the manifold was filled with SF₄ from a metalcylinder to produce a pressure of 18 psia and SF₄ (13 psia, 37 mmol) wasintroduced into the flask. The residual SF₄ in the ballast was pumpedthrough a soda-lime trap. The solution of 2° amine in Et₂O/TEA was thenadded dropwise to the SF₄ solution and stirred. The −78° C. bath wasreplaced by a −10° C. bath and the mixture was stirred for 3 h. Aftercooling to −78° C., excess SF₄ was pumped out of the solution through asoda-lime trap and the solution was brought to room temperature. WhenEt₂O was used as solvent, an H-tube was attached to the flask and thesolvent decanted into one arm of the H-tube. This was followed byfiltration of the solution to remove precipitated TEA-HF. The filtratewas then evaporated in-vacuo. After the solvent was completely removed,the H-tube was taken into a dry-box and the product was transferred to aTeflon bottle. When THF was used as solvent, an in-vacuo evaporation ofthe solvent was first carried out and the residue was redissolved intoEt₂O and further processed as above ¹H and ¹⁹F NMR of samples were donein teflon NMR tubes.

The following compositions were obtained via this procedure:diphenylaminosulfur trifluoride (2), ¹H NMR (CDCl₃) δ7.5-7.3 (m, 10H),¹⁹F NMR (CDCl₃) δ69.5 (d, 2F), 31 (t,1F).4,4′-dimethyl-diphenylamino-sulfur trifluoride (4).¹H NMR (CDCl₃)δ7.35-7.10 (m, 8H), 2.35 (s, 6H).¹⁹F NMR (CDCl₃) δ68.25 (d, 2F), 32.0(t, 1 F).4,4′-dimethoxy-diphenylaminosulfur trifluoride (6).¹H NMR(CDCl₃) δ7.25 (d, 4H), 7.35 (d, 4H), 3.8 (s, 6H).¹⁹F NMR (CDCl₃) δ68.5(s, br, 2F), 31.75 (s, br, 1F).N-4-chlorophenyl-N-phenylaminosulfurtrifluoride (8).¹H NMR (CDCl₃) δ7.5-7.25 (m, 9H), ¹⁹F NMR (CDCl₃) δ70(d, 2F), 31 (t, 1F).N-naphthyl-N-phenyl-aminosulfur trifluoride (10).¹HNMR (CDCl₃) δ8.4 (d, 0.66H), 8.15 (d, 0.34H), 7.9-6.8 (m, 11H), ¹⁹F NMR(CDCl₃) δ71, 66.5 (2(d) 0.66F), 70, 67.5 (2(d), 134F) 33 (t,1F).Indolineaminosulfur trifluoride (27).¹H NMR (CDCl₃) δ7.4 (d, 1H),7.2 (dd, 2H), 7.0 (d, 1H), 4.3 (t, 2H), 3.1 (t, 2H).¹⁹F NMR (CDCl₃) δ60(br, s, 2F), 20 (br, s, 1F).3,4-dihydro-2H-1,4-benzoxazinesulfurtrifluoride (29).¹H NMR (CDCl₃) δ7.3-7.1 (m, 2H), 6.8-7.1 (m, 2H),4.5-4.3 (t, 2H), 4.2-3.9 (t, 2H).¹⁹F NMR (CDCl₃) δ63 (br, s, 2F) 11 (br,s, 1F). N-methyl-N-phenylamionsulfur trifluoride (31).¹H NMR (CDCl₃)δ7.5-7.3 (m, 3H), 7.3-7.0 (m, 2H) 3.4 (s, 3H) ¹⁹F NMR (CDCl₃) δ64 (2F)δ26 (1F).N-ethyl-N-phenyl aminosulfur trifluoride(33)²⁵.N-2-methoxyethyl-N-phenylaminosulfur trifluoride (35) ¹H NMR(CDCl₃) δ7.5-7.35 (m, 3H), 7.35-7.20 (m, 2H), 4.1-3.9 (m, 2H), 3.7-3.5(m, 2H), 3.30 (s, 3H) ¹⁹F NMR (CDCl₃) δ63 (br, s, 2F), 31.5 (br, s,1F).N-2-methoxyethyl-N-methylaminosulfur trifluoride (37).¹H NMR (CDCl₃)δ3.8-3.3 (m, 4H), 3.15 (s, 3H), 2.95 (s, 3H) ¹⁹F NMR (CDCl₃) δ56 (s, br,2F), 23 (s, br, 1F).(S)-2-(methoxymethyl)pyrrolidin-1-yl sulfurtrifluoride (39)²⁶.bis(2-methoxyethyl)aminosulfur trifluoride (41) ¹HNMR (CDCl₃).δ3.5 (t, 4H), 3.15 (t, 4H), 3.05 (s, 6H) ¹⁹F NMR (CDCl₃) δ55(s, br, 2F) 28 (s, br, 1F).

Present Fluorination Method with Novel Aminosulfur Trifluorides

The fluorination reactions of target compounds with the aminosulfurtrifluorides are conducted by charging the reaction vessel with thesubstrate first then adding the aminosulfurtrifluoride or charging thevessel first with the aminosulfur trifluoride then adding the substrate.Alternatively, both may be charged simultaneously. Solvents may or maynot be used. Solvents include materials which will not react with theaminosulfur trifluoride or substrate. These include hydrocarbons e.g.hexane, halocarbons e.g., CH₂Cl₂, ethers, such as diethyl ethe,rnitriles ,such as acetonitrile, nitro compounds e.g. nitromethane.

The fluorination reactions are usually conducted under anhydrousconditions in metal, glass, plastic or ceramic vessels. The fluorinationreaction temperature is conducted at any temperature between thefreezing point of the solvent and the boiling point of the solvent.Pressure is usually not necessary and reactions are mostly carried outat ambient or autogeneous pressure.

The fluorination products can be separated from the reaction mixture andthen purified by standard methods including distillation,chromatography, solvent extraction and recrystallization.

In general, with the aminosulfurtrifluoride compositions of the presentinvention higher yields and selectivities to the desired fluoroproductswere realized, for alcohol and ketone substrates, as compared to thoserealizable under the same conditions with thedialkylaminosulfurtrifluorides.

Fluorination of the 1°alcohol, phenethanol was also easily accomplished.For example reaction of this compound with Ph₂NSF₃ and (MeOCH₂CH₂)₂NSF₃produce phenethyl fluoride in 60 and 68% yield respectively.

Fluorination of the 3°alcohol, ethyl-2-hydroxybutyrate with Ph(Me)NSF₃afforded a 90% yield of ethyl-2-fluorobutyrate. Similar results wereobtained with bismethoxyethyl aminosulfur trifluoride. With the3°alcohol, acetone cyanohydrin a 66% yield of2-fluoro-2-methylpropionitrile was obtained on reaction with Ph(Me)NSF₃.

Aldehydes and ketones react with the aminosulfur trifluorides to effecta replacement of the oxygen atom by two fluorine atoms. For examplebenzaldehyde reacted with either Ph₂NSF₃ or (MeOCH₂CH₂)₂NSF₃ to producebenzal fluoride (PhCHF₂) in quantitative yields. The dialdehyde,terephthaldehyde reacted with Ph(Me)NSF3 to afford a 95% yield of1,′1,′4,′4′-tetrafluoro-p-xylene after 16 h at room temperature inCH₂Cl₂. This product was obtained in 98% yield on reaction with(MeOCH₂CH₂)₂NSF₃ in refluxing CH₂Cl₂ after 5 h while an 86% yield wasobtained on reaction with Ph(Me)NSF₃ in CH₂Cl₂ at room temperature after69 h.

Other ketones also afforded the corresponding gem-difluoro product onreaction with the aminosulfur trifluorides. For example 4-carboethoxycyclohexanone react with Ph(Me)NSF3 and N4-chlorophenyl-N-phenylaminosulfur trifluoride to produce1-carboethoxy-4,4-diflurocyclohexanone in CH₂Cl₂ in 70% and 95% yieldsrespectively. Also a 30% yield of difluorocyclooctane was obtained onreaction of cyclooctanone with Ph₂NSF₃ at room temperature after 7 daysin CH₂Cl₂.

When the compound is a ketone, at least a catalytic amount of HF can beadded to the fluorination. The HF may be added as the neat liquid or gasor as an adduct with a base, as with HF.pyridine.

Carboxylic acids react with aminosulfur trifluorides to producecarboxylic acid fluorides. For example benzoic acid reacts with Ph₂NSF₃to produce benzoyl fluoride in quantitative yield.

Carboxylic acid chlorides react with aminosulfur trifluorides to produceacid fluorides. For example (MeOCH₂CH₂)₂NSF₃ react with benzoic acid togenerate benzoyl fluoride in quantitative yield.

Sulfoxides react with aminosulfur trifluorides to afforda-fluorosulfides. For example phenyl methyl sulfoxide gave fluoromethylphenyl sulfide in 70% yield on reaction with (MeOCH₂CH₂)₂NSF₃.

Epoxides react with aminosulfur trifluorides to produce thecorresponding vicinal difluoride. For example cyclohexene oxide reactswith bis(2-methoxyethyl)aminosulfur trifluoride in CH₂Cl₂ containing acatalytic quantity of HF to afford 1,2-difluorocyclohexane in 33% yield.

It was found that the deoxofluorination of ketones by Ph(Me)NSF₃ areconsiderably accelarated in the presence of Lewis acids as catalysts. Nosuch rate increase was observed with Et₂NSF₃ (prior art DAST). Forexample in the synthesis of 1-t-butyl-4,4-difluorocyclohexane from4-t-butylcyclohexanone and Ph(Me)NSF₃ a quantitative yield was obtainedin the presence of 0.1 equivalent of BF₃.OEt₂ after 16 h . In theabsence of BF₃.OEt₂ the reaction took 69 h for complete conversion ofthe starting material to product. A similar accelaration of thisreaction was observed with Znl₂ and TiCl₄. No increase in rate withadded Lewis acids was observed when the fluorination of4-t-butylcyclohexanone was carried out with Et₂NSF₃ (prior art DAST).These results indicate that Ph(Me)NSF₃ may be useful for fluorinatingunreactive ketones.

In an examplary fluorination of the present invention, deoxofluorinationof cyclooctanol with diarylaminosulfur trifluorides proceeds rapidly at−78° C. in CH₂Cl₂ to produce cyclooctylfluoride and cyclooctene with theformer predominating (Table 6). Differing ratios of fluoride to olefinwere observed with the various aromatic substituted trifluorides. Thesterically hindered N-naphthyl-N-phenylaminosulfur trifluoride reactedquite slowly affording only a 10% conversion of starting material toproducts after 16 h at room temperature. A rapid conversion to themonofluoride was obtained with N-methyl-N-phenylaminosulfur trifluoride.Among the alkoxyalkyl compositions 35-41 (Table 4), the phenylsubstituted aminosulfur trifluoride (35) proved to be the most reactiveaffording fluorination at −78° C. in 1 h as compared to the methyl andbisalkoxyalkyl compositions (37, 41, respectively) which required longerreaction times (˜3 hr) at −78° C. to effect the same conversion.

EXAMPLE 2 Reaction of Cyclooctanol with the New Aminosulfur Trifluorides

A solution of cyclooctanol (128 mg, 1 mmol) in CH₂Cl₂ (3.0 mL) was addedto a solution of aminosulfur trifluoride per Table 6 (1 mmol) in CH₂Cl₂(2.0 mL) at −78° C. under N₂ in a 3-neck flask equipped with N₂ inlet,septum, and a magnetic stirring bar. The reaction was monitored byG.C.M.S. for disappearance of the starting material. On completion, themixture was poured into satd. NaHCO₃ (25 mL) and after CO₂ evolutionceased, it was extracted into CH₂Cl₂ (3×15 mL), dried (Na₂SO₄), filteredand evaporated in vacuo to obtain the product as a mixture of cyclooctylfluoride and cyclooctene. Flash chromatography on silica gel in hexaneafforded the pure products.

The aminosulfur trifluoride is synthesized by reaction of a secondaryamine with SF₄ in a non-aqueous solvent that will not react chemicallywith SF₄ or the aminosulfur trifluoride product. Examples includeethers, e.g., ethylether (Et₂O), tetrahydrofuran (THF), halogenatedhydrocarbons, e.g., CH₂Cl₂, freons, hydrocarbons, e.g., toluene, hexane,tertiary amines, liquid SO₂ and supercritical CO₂.

The reaction can be carried out at temperatures ranging from −90° C. orthe freezing point of the solvent to the boiling point of the solvent.

The reaction mixture may be homogenous or heterogenous.

The secondary amine is represented by R¹R²NH. R¹=alkyl (cyclic ornon-cyclic, with or without heteroatoms), aryl, or alkoxyalkyl. R²=alkyl(cyclic or non-cyclic, with or without heteroatoms), aryl oralkoxyalkyl. R⁻¹ may or may not be the same as R².

The tertiary amine is represented by R¹R²R³N. R¹, R² or R³=alkyl (cyclicor non-cyclic, with or without heteroatoms), or aryl. This includestertiary amines which contain the N-atom in a ring, e.g.,N-methylpiperidine or in a chain, e.g., triethylamine. It also includestertiary amines which contain the N-atom at a bridge-head, e.g.,quinuclidine or triethylene diamine and in fused rings, e.g.,diazabicycloundecane (DBU). Compounds containing >1, tertiary aminegroup in the molecule can also be used. The tertiary amine could alsofunction as the reaction solvent. Examples of specific amines employedfor the synthesis of R₂NSF₃ reagents should also be effective for the insitu process described below.

No aminosulfur trifluoride product was obtained when pyridine or3-methylpyridine was used instead of a tertiary amine; however, morebasic pyridines than the latter are expected to be useful.

No aminosulfur trifluoride product was obtained when NaF or CsF was usedinstead of a tertiary amine. Thus, its utilization in the process beyondsimply acting as an HF acceptor is an essential feature of theinvention.

The substrate for fluorination may be an alcohol, an aldehyde, ketone,carboxylic acid, aryl or alkyl sulfonic acid, aryl or alkyl phosphonicacid, acid chlorides, silyl chlorides, silyl ethers, sulfides,sulfoxides, epoxides, phosphines and thiophosphines.

Water or a low molecular weight alcohol (CH₃OH, C₂H₅OH, etc.) may beadded to hydrolyze the intermediate sulfinyl fluoride for disposal andto generate the starting secondary amine.

The fluorinated product may be separated from the aqueous acidic mixtureby extraction into a water immiscible organic solvent.

The desired product may be distilled and thus isolated from the crudereaction mixture.

TABLE 6 Deoxofluorination of cyclooctanol

Ratio of cyclooctyl Aminosulfur trifluoride Reaction conditionsfluoride/cycloctene

CH₂Cl₂, −78° C. 1 h 70:30

CH₂Cl₂, −78° C. 1 h 90:10

CH₂Cl₂, −78° C. 1 h 76:24

CH₂Cl₂, −78° C. 1 h 94:6 

CH₂Cl₂, RT 16 h, 10% conversion

CH₂Cl₂, −78° C. 1 h 99:1 

CH₂Cl₂, −78° C. 1 h 90:10 CH₃N(SF₃)CH₂CH₂OMe CH₂Cl₂, −78° C. 85:15 37 3h MeOCH₂CH₂N(SF₃)CH₂CH₂OMe CH₂Cl₂, −78° C. 85:15 41 3 h

CH₂Cl₂, −78° C. 8 h 17:6  (C₂H₅)₂NSF₃ CCl₃F 70:30

In contrast to the superior deoxofluorination of cyclooctanol for thereagents reported in Table 6, (S)-2-(methoxyethyl)pyrrolidin-1-yl-sulfurtrifluoride was a poor deoxofluorination reagent for cyclooctanol. In areaction carried out at −78° C. in CH₂Cl₂ for 8 h only 17% cyclooctylfluoride was produced and 6% cyclooctene, as determined by nuclearmagnetic resonance.

Table 6 summarizes the results obtained on fluorination of 4-t-butylcyclohexanone with the aminosulfur trifluorides. All of the compositionsexamined except N-naphthyl-N-phenylaminosulfur trifluoride converted theketone to a mixture of 4-t-butyl-difluorocyclohexane and4-t-butyl-1-fluorocyclohexene, with the former predominating. Thefluorination of this ketone was much slower than observed for thefluorination of cyclooctanol. A complete conversion to the fluorinatedproducts required several days at room temperature in CH₂Cl₂. However,addition of a catalytic amount of HF (generated in-situ from EtOH)accelerated the rate of reaction considerably. The reaction time wasreduced from several days to ˜16 h when the diaryl, arylalkyl, andN-methoxyethyl-N-phenylaminosulfur trifluorides were reacted with4-t-butylcyclohexanone in the presence of HF. The effect of HF onreaction rate was, however, less pronounced with the alkoxyalkylaminosulfur trifluorides 37 and 41. A reasonable reaction time (40 h)for complete fluorination of the ketone withbis(methoxyethyl-aminosulfur trifluoride (41) was obtained when thereaction was carried out at 40° C.

EXAMPLE 3 Reaction of 4-t-Butylcyclohexanone with AminosulfurTrifluorides

A solution of 4-t-butylcyclohexanone (1.0 mmol) in CH₂Cl₂ (3.0 mL)contained in a 25 mL teflon vessel equipped with a swagelok stopper, N₂inlet tube, and stirring bar was treated with a solution of aminosulfurtrifluoride per Table 7 (1.8 mmol) in CH₂Cl₂ (2.0 mL) at roomtemperature. EtOH (11 mg, 14 μL, 0.2 mmol) was added and the mixture wasstirred at room temperature. The progress of the reaction was monitoredby a G.C.M.S. On completion, the solution was poured into satd. NaHCO₃and after CO₂ evolution ceased, it was extracted into CH₂Cl₂ (3×15 mL),dried (Na₂SO₄), filtered, and evaporated in vacuo to afford a mixture of4-t-butyl-difluorocyclohexane and 4-t-butyl-1-fluorocyclohexene.

TABLE 7 Deoxofluorination of 4-t-butylcyclohexanone

Ratio of difluoride/vinyl Aminosulfur trifluoride Reaction conditionsfluoride

CH₂Cl₂, RT, 5 days 96:4 

CH₂Cl₂, RT, EtOH(0.2 eq), 16 h 88:12

CH₂Cl₂, RT, EtOH(0.2 eq), 16 h 82:18

CH₂Cl₂, RT, EtOH(0.2 eq), 16 h 89:11

CH₂Cl₂, RT, 5 days 86:14

CH₂Cl₂, RT, EtOH(0.2 eq), 16 h 86:14 CH₃N(SF₃)CH₂CH₂OMe CH₂Cl₂, RT,81:19 EtOH(0.2 eq), 16 h MeOCH₂CH₂N(SF₃)CH₂CH₂OMe CH₂Cl₂, 40° C., 81:19EtOH(0.2 eq), 40 h Et₂NSF₃(DAST) CH₂Cl₂, RT, 67/33 EtOH(0.2 eq), 16 h

A convenient and economically attractive method for deoxofluorination ofthe alcohol (cyclooctanol) and ketone (4-t-butylcyclohexanone) wasachieved by conducting the reaction in the medium used for preparationof the reagent, i.e., without isolating the aminosulfur trifluoride.

Schematic representation of the in-situ fluorination process:

EXAMPLE 4 Deoxofluorination Conducted In-Situ without Isolation ofAminosulfur Trifluoride

A solution of diphenylamine (25 mmol) in THF (25 mL) containingtriethylamine (3.48 mL, 25 mmol) was added dropwise to a solution of SF₄(37 mmol) in THF (75 mL) contained in a 3-neck flask equipped with astirring bar, N₂ inlet tube, dry ice condenser, and SF₄ inlet tube (asdescribed above) at −78° C. The mixture was brought to −10° C. and keptfor 3 h. It was again cooled to −78° C. and excess SF₄ was removedin-vacuo. The mixture was then treated with a THF (10 mL) solution ofcyclooctanol (3.20 g, 25.0 mmol) and stirred at −78° C. for 1 h. Thereaction was quenched with 5 mL H₂O and the solvents were evaporatedin-vacuo, treated with satd. NaHCO₃ (200 mL), extracted into EtOAc,dried (MgSO₄), filtered, and evaporated in-vacuo to obtain the productas a mixture of cyclooctyl fluoride and cyclooctene (70:30 ratio).

EXAMPLE 5

A solution of diphenylaminosulfur trifluoride (25 mmol) in THF (100 mL)prepared as above was treated with a THF solution (10 mL) of4-t-butylcyclohexanone (3.85 g, 25 mmol) at room temperature and stirredfor 7 days. After work-up as described for the alcohol above, a productwas obtained which was a mixture of 4-t-butyl-difluorocyclohexane and4-t-butyl-1-fluorocyclohexene (96:4 ratio).

Additional examples of the fluorination method of the present inventionwith various target compounds to be fluorinated are set forth below.

EXAMPLE 6 Fluorination of Phenethanol

A solution of phenethanol (122 mg, 1 mmol) in CH2Cl2 (5.0 mL) was addedto diphenylaminosulfur trifluoride (308 mg, 1.2 mmol) at −78° C.; underN2; then brought to room temperature and stirred for 16 h. After work-upand purification as above phenethyl fluoride (75 mg, 60%) was obtained.¹H NMR in CDCl₃ d 7.7-7.4 (d, 2H), 7.3-7.1 (t, 2H), 7.1-7.0 (t,1 H). ¹⁹F(CDCl₃) d −215 (2F).

EXAMPLE 7 Fluorination of Phenethanol

A solution of phenethanol (122 mg, 1 mmol) in CH₂Cl₂ (5.0 mL) was addedto bismethoxyethyl aminosulfur trifluoride (265 mg, 1.2 mmol) at −78°C.; under N₂; then brought to room temperature and stirred for 16 h.After work-up and purification as above phenethyl fluoride (85 mg, 68%)was obtained. ¹H NMR in CDCl₃ d 7.7-7.4 (d, 2H), 7.3-7.1 (t, 2H),7.1-7.0 (t, 1H). ¹⁹F (CDCl₃) d −215 (2F).

EXAMPLE 8 Fluorination of ethyl-2-hydroxybutyrate

A solution of ethyl-2-hydroxybutyrate (397 mg, 3 mmol) in CH₂Cl₂ (5.0mL) was added to N-methyl-N-phenylaminosulfur trifluoride (877 mg, 4.5mmol) at −78° C.; under N₂ and stirred for 16 h. After work-up andpurification as above ethyl-2-fluorobutyrate (362 mg, 90%) was obtained.¹H NMR in CDCl₃ d 4.3-4.1 (q, 2H), 1.55 (d,6H), 1.3-1.1 (t,3H). ¹⁹F(CDCl₃) d −148 (1F).

EXAMPLE 9 Fluorination of ethyl-2-hydroxybutyrate

A solution of ethyl-2-hydroxybutyrate (397 mg, 3 mmol) in CH₂Cl₂ (5.0mL) was added to bis(methoxyethyl)aminosulfur trifluoride (994 mg, 4.5mmol) at −78° C.; under N₂ and stirred for 16 h. After work-up andpurification as above ethyl-2-fluorobutyrate (362 mg, 90%) was obtained.¹H NMR in CDCl₃ d 4.3-4.1 (q, 2H), 1.55 (d,6H), 1.3-1.1 (t,3H). ¹⁹F(CDCl₃) d −148 (1F).

EXAMPLE 10 Fluorination of Acetone Cyanohydrin

A solution of acetone cyanohydrin (87 mg, 1 mmol) in CH₂Cl₂ (10.0 mL)was added to N-methyl-N-phenylaminosulfur trifluoride (292 mg, 1.5 mmol) at −78° C.; under N₂; then brought to room temperature and stirred for16 h. After work-up and purification as above2-fluoro-2-methylpropionitrile (59 mg, 90%) was obtained. ¹H NMR in(CDCl₃) d 1.75 (d, 6H). ¹⁹F (CDCl₃) d −138 (1F).

EXAMPLE 11 Fluorination of 4-carboethoxycyclohexanone

A solution of 4-carboethoxycyclohexanone (170 mg, 1 mmol) in CH₂Cl₂ (5.0mL) was added to N-methyl-N-phenylaminosulfur trifluoride (390 mg, 2.0mmol) at −78° C.; under N₂; then brought to room temperature and stirredfor 16 h. After work-up and purification as above1-carboethoxy-4,4-difluorocyclohexanone (134 mg, 70%) was obtained. ¹HNMR in CDCl₃ d 5.3-5.1 (m, 1H), 4.3-4.0 (q, 2H ), 2.7-1.6 (m, 8H), 1.25(t, 3H). ¹⁹F (CDCl₃) d −94 (1F,dd) −100.5 (dd, 1F).

EXAMPLE 12

A solution of 4-carboethoxycyclohexanone (170 mg, 1 mmol) in CH₂Cl₂ (5.0mL) was added to N-phenyl-N-4-chlorophenyl aminosulfur trifluoride (584mg, 2.0 mmol ) at −78° C.; under N₂; then brought to room temperatureand stirred for 16 h. After work-up and purification as above1-carboethoxy-4,4-difluorocyclohexanone (134 mg, 70%) was obtained. ¹HNMR in CDCl₃ d 5.3-5.1 (m, 1H), 4.3-4.0 (q, 2H ), 2.7-1.6 (m, 8H), 1.25(t, 3H). ¹⁹F (CDCl₃) d −94 (1F, dd) −100.5 (dd, 1F).

EXAMPLE 13 Fluorination of Cyclooctanone

A solution of cyclooctanone (3.20 g, 25 mmol) in CH₂Cl₂ (5.0 mL) wasadded to diphenylaminosulfur trifluoride (6.43 g, 25 mmol ) at roomtemperature under N₂; and stirred for 7 days. After work-up as abovedifluorcyclooctanone was obtained in 30% yield (by g.c.) ¹⁹F (CDCl₃) d−99.5 (2F).

EXAMPLE 14 Fluorination of Benzaldehyde

A solution of benzaldehyde (106 mg, 1 mmol) in CH₂Cl₂ (5.0 mL) was addedto diphenyl aminosulfur trifluoride (386 mg, 1.0 mmol ) at −78° C.;under N₂; then brought to room temperature and stirred for 16 h. Afterwork-up and purification as above benzal fluoride (128 mg, quantitativeyield) was obtained. ¹H NMR in CDCl3 d 7.65 (d, 2H ), 7.4 (t, 1H), 7.3(t, 2H). ¹⁹F (CDCl₃) d −110 (2F).

EXAMPLE 15

A solution of benzaldehyde (106 mg, 1 mmol) in CH₂Cl₂ (5.0 mL) was addedto bis(methoxyethyl) aminosulfur trifluoride (332 mg, 1.5 mmol ) at −78°C.; under N₂; then brought to room temperature and stirred for 16 h.After work-up and purification as above benzal fluoride (128 mg,quantitative yield) was obtained. ¹H NMR in CDCl₃ d 7.65 (d, 2H ), 7.4(t, 1H), 7.3 (t, 2H). ¹⁹F (CDCl₃) d −110 (2F).

EXAMPLE 16 Fluorination of Benzoic Acid

A solution of benzoic acid (122 mg, 1 mmol) in CH₂Cl₂ (5.0 mL) was addedto diphenylaminosulfur trifluoride (771 mg, 3.0 mmol ) under N₂ andstirred for 16 h at room temperature. After work-up as above benzoylfluoride (124 mg, quantitative yield) was obtained. The product wasidentified by g.c.m.s. M⁺=124

EXAMPLE 17 Fluorination of Benzoyl Chloride

A solution of benzoyl chloride (141 mg, 1 mmol) in CH₂Cl₂ (5.0 mL) wasadded to bis(methoxyethyl)aminosulfur trifluoride (567 mg, 3.0 mmol )under N₂ and stirred for 16 h at room temperature. After work-up asabove benzoyl fluoride (124 mg, quantitative yield) was obtained. Theproduct was identified by g.c.m.s. M⁺=124

EXAMPLE 18 Fluorination of Phenyl Methyl Sulfoxide

A solution of methyl phenyl sulfoxide (140 mg, 1 mmol) in CH₂Cl₂ (5.0mL) was added to bis(methoxyethyl)aminosulfur trifluoride (332 mg, 1.5mmol ) under N₂ and stirred for 16 h at room temperature. After work-upas above fluoromethyl phenyl sulfide (70% yield as determined by NMR)was obtained. ¹H NMR (CDCl₃) d 7.5-7.0 (m, 5H), 3.3 (d, 2H). 19F

NMR (CDCl₃) d −183 (1F).

EXAMPLE 19 Fluorination of Cyclohexene Oxide

20 mmol of cyclohexene oxide and 24 mmol of Deoxofluor were charged to a100 mL three neck, round bottom flask equipped with a stir bar, acondenser, a glass stopper, a gas inlet adapter and a septum. 4 mmol ofethanol was added to generate HF in-situ. The flask was heated to 60-70C. for 30 h under N2. The reaction mixture was diluted in chloroformwashed with saturated bicarbonate, dried Na2SO4), filtered andevaporated in vacuo. GC-MS indicated >95% conversion of the startingmaterial to products. Two major products were observed in the ¹⁹F NMR. Amultiplet was observed at −193 ppm and another multiplet at −182 ppm.These signals agree with literature values for 1,2 difluorocyclohexaneand bis (fluorocyclohexyl) ether respectively. Integration of peaksindicate a product ratio of 1:2 difluoride/difluoroether

EXAMPLE 20 Fluorination of 4-t-butylcyclohexanone by diethylaminosulfurtrifluoride(DAST) and N-ethyl-N-phenylaminosulfur trifluoride (acomparison) (a) Fluorination with DAST

A solution of 4-t-butylcyclohexanone (308 mg, 2.0 mmol) in CH₂Cl₂ (10.0mL) was added to diethylaminosulfur trifluoride (483 mg, 3.0 mmol ) atroom temperature under N₂. BF₃.OEt₂ (100 mL) was added and the mixturewas stirred for 6 h at room temperature. The mixture was washed withsaturated NaHCO₃, dried (Na₂SO₄), filtered and evaporated in vacuo.Proton and Fluorine NMR with 4-fluoroanisole (2 mmol) as internalstandard showed that a 67% yield of 1,1-difluoro-4-t-butylcyclohexanewas obtained.

(b) Fluorination with N-ethyl-N-phenylaminosulfur trifluoride

A solution of 4-t-butylcyclohexanone (308 mg, 2.0 mmol) in CH₂Cl₂ (10.0mL) was added to N-ethyl-N-phenylaminosulfur trifluoride (627 mg, 3.0mmol ) at room temperature under N₂. BF₃.OEt₂ (100 mL) was added and themixture was stirred for 6 h at room temperature. The mixture was washedwith saturated NaHCO₃, dried (Na2SO4), filtered and evaporated in vacuo.Proton and Fluorine NMR with 4-fluoroanisole (2 mmol) as internalstandard showed that a 99% yield of 1,1-difluoro-4-t-butylcyclohexanewas obtained.

EXAMPLE 21 Catalysis of fluorination by Lewis acids usingN-methyl-N-phenylaminosulfurtrifluoride (a comparison) (a) Fluorinationof 4-t-butylcyclohexanone without Lewis Acid Catalyst

A reaction of 4-t-butylcyclohexanone (2 mmol) withN-methyl-N-phenylaminosulfur trifluoride (3.0 mmol) in CH₂Cl₂ (10 mL) atroom temperature gave a 99% conversion to1,1-difluoro-4-t-butylcyclohexane after 69 h. as determined by NMR(4-fluoroanisole as internal standard)

(b) With BF₃.OEt₂ as Catalyst

A reaction of 4-t-butylcyclohexanone (2 mmol) withN-methyl-N-phenylaminosulfur trifluoride (3.0 mmol) in CH₂Cl₂ (10 mL)containing BF₃.OEt₂ (0.3 mmol) at room temperature gave a 99% conversionto 1,1-difluoro-4-t-butylcyclohexane after 6 h. as determined by NMR(4-fluoroanisole as internal standard)

(c) With Znl₂ as Catalyst

A reaction of 4-t-butylcyclohexanone (2 mmol) withN-methyl-N-phenylaminosulfur trifluoride (3.0 mmol) in CH₂Cl₂ (10 mL)containing Znl₂ (0.3 mmol) at room temperature gave a 67% conversion to1,1-difluoro-4-t-butylcyclohexane after 3 h. as determined by NMR(4-fluoroanisole as internal standard)

(d) With TiCl₄ as Catalyst

A reaction of 4-t-butylcyclohexanone (2 mmol) withN-methyl-N-phenylaminosulfur trifluoride (3.0 mmol) in CH₂Cl₂ (10 mL)containing TiCl₄ (0.3 mmol) at room temperature gave a 67% conversion to1,1-difluoro-4-t-butylcyclohexane after 3 h. as determined by NMR(4-fluoroanisole as internal standard).

EXAMPLE 22 Reaction of diethylaminosulfur trifluoride with4-t-butylcyclohexanone (with and without Lewis acids) (a) Without LewisAcid

A reaction of 4-t-butylcyclohexanone (2 mmol) with diethylaminosulfurtrifluoride (3.0 mmol) in CH₂Cl₂ (10 mL) at room temperature gave a 99%conversion of starting material to products and a 67% yield of1,1-difluoro-4-t-butylcyclohexane after 6 h. as determined by NMR(4-fluoroanisole as internal standard).

(b) With BF₃.OEt₂ as Catalyst

A reaction of 4-t-butylcyclohexanone (2 mmol) with diethylaminosulfurtrifluoride (3.0 mmol) in CH₂Cl₂ (10 mL) containing BF3.OEt2 (0.3 mmol)at room temperature gave a 99% conversion of starting material toproducts and a 67% yield of 1,1-difluoro-4-t-butylcyclohexane after 6 h.as determined by NMR (4-fluoroanisole as internal standard).

(c) With Znl₂ as Catalyst

A reaction of 4-t-butylcyclohexanone (2 mmol) with diethylaminosulfurtrifluoride (3.0 mmol) in CH₂Cl₂ (10 mL) containing Znl2 (0.3 mmol) atroom temperature gave a 99% conversion of starting material to productsand a 67% yield of 1,1-difluoro-4-t-butylcyclohexane after 6 h. asdetermined by NMR (4-fluoroanisole as internal standard).

(d) With TiCl₄ as Catalyst

A reaction of 4-t-butylcyclohexanone (2 mmol) with diethylaminosulfurtrifluoride (3.0 mmol) in CH₂Cl₂ (10 mL) containing TiCl₄ (0.3 mmol) atroom temperature gave a 99% conversion of starting material to productsand a 67% yield of 1,1-difluoro-4-t-butylcyclohexane after 6 h. asdetermined by NMR (4-fluoroanisole as internal standard).

The present invention provides a high yielding, preferably one-step,process for the preparation of a number of classes of novel aminosulfurtrifluoride compounds. These novel aminosulfur trifluoride compoundshave been shown to have unique performance for effectingdeoxofluorination of alcohols and ketones as demonstrated by thepresently reported thermal analysis studies indicating that they aresafer to use than the currently available dialkylaminosulfurtrifluorides (DAST), see the data in Table 5 for gas pressure generatedper millimole of reagent decomposed, and more effective at fluorinatingalcohols than (S)-2-(methoxyethyl)pyrrolidin-1-yl sulfur trifluoride,see Table 6 for the efficiency of fluorination showing poor fluorinationby the latter compound in contrast to the compounds of the presentinvention.

The simplicity of the method used for preparing the new aminosulfurtrifluorides combined with their safety and simplicity in use shouldmake these compounds attractive for large scale commercial productionand use, providing unexpected improvement in fluorination technology incontrast to the industry avoidance of DAST for such fluorinations.

The present invention has been set forth with regard to severalpreferred embodiments, but the full scope of the present inventionshould be ascertained from the claims which follow.

We claim:
 1. A method for the fluorination of a compound selected fromthe group consisting of alcohols, aldehydes, ketones, epoxides, andmixtures thereof, using a fluorinating reagent comprising contactingsaid compound with said fluorinating reagent under conditions sufficientto fluorinate said compound wherein said fluorinating reagent is anaminosulfur trifluoride composition having a structure with one or more:

wherein m=1-5 and R¹ and R² are: (1) when m=1, individually aryl ormeta- or para-substituted aryl radicals in which the meta- orpara-substitution is selected from the group consisting of normal andbranched C₁₋₁₀, trifluoromethyl, alkoxy, aryl C₆₋₁₀, nitro, sulfonicester, N,N-dialkylamino and halogens; or (2) when m=1, individually arylradicals which are fused or linked to one another, or (3) when m=1,together an unsaturated cyclic ring having 2 to 4 carbon ring membersand one to three heteroatoms selected from the group consisting ofoxygen, nitrogen, protonated nitrogen and alkylated nitrogen whereinsaid ring has one to three functional groups selected from hydrogen,normal and branched C₁₋₁₀ alkyl, haloalkyl, aryl halogen, cyano, nitroand amino; or (4) when m=2-5, R¹ is a single phenyl radical linked toeach —NSF₃ radical and R² is an aryl radical having C₆ to C₁₀; or (5)when m=2-5, R¹ and R² are individually divalent aryl radicals of C₆ toC₁₀ linked to adjacent —NSF₃ radicals except R¹ and R² are monovalentaryl radicals having C₆ to C₁₀ where R¹ and R² are linked to only one—NSF₃ radical; or (6) when m=1, one of R¹ and R² is an aryl radical andthe other is an alkyl radical of C₁₋₁₀.
 2. The method of claim 1 whereinsaid compound is selected from the group consisting of alcohols andmixtures thereof.
 3. The method of claim 1 wherein said alcohol isselected from the group consisting of monofunctional and polyfunctionalprimary, secondary, tertiary and vinyl alcohols and mixtures thereof. 4.The method of claim 1 wherein said aldehyde is selected from the groupconsisting of aliphatic, aromatic and heterocyclic aldehydes andmixtures thereof.
 5. The method of claim 1 wherein said ketone isselected from the group consisting of aliphatic, aromatic andheterocyclic ketones and mixtures thereof.
 6. The method of claim 1wherein said epoxide is selected from the group consisting of aliphatic,aromatic and heterocyclic epoxide and mixtures thereof.
 7. The method ofclaim 1 wherein said fluorination is conducted in the presence of asolvent.
 8. The method of claim 7 wherein said solvent is selected fromthe group consisting of paraffins, halocarbons, ethers, nitrites, nitrocompounds and mixtures thereof.
 9. The method of claim 7 wherein saidfluorination is conducted at a temperature above the freezing point ofsaid solvent and below the boiling point of said solvent.
 10. The methodof claim 1 wherein the fluorination is conducted under anhydrousconditions.
 11. The method of claim 1 wherein said compound is a ketoneand the fluorination is catalyzed with at least a catalytic amount of aLewis acid.
 12. The method of claim 11 wherein said Lewis acid isselected from the group consisting of BF₃, Znl₂, TiCl₄ and mixturesthereof.
 13. The method of claim 1 wherein said compound is a ketone andat least a catalytic amount of HF is added to said fluorination.
 14. Amethod of claim 1 comprising synthesizing said aminosulfur trifluoridecomposition from a secondary amine and SF₄ in a reaction media andwithout isolating said aminosulfur trifluoride composition, fluorinatingsaid compound with said aminosulfur trifluoride composition by contactof said compound with said aminosulfur trifluoride in said reactionmedia.
 15. The method of claim 14 wherein a tertiary amine is presentduring the synthesizing of said aminosulfur trifluoride.
 16. The methodof claim 15 wherein a solvent is present during the synthesizing of saidaminosulfur trifluoride.